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dc.contributor.authorSmalley, KSMen_US
dc.contributor.authorEisen, TGen_US
dc.identifier.citationMELANOMA RESEARCH, 2002, 12 pp. 187 - 192en_US
dc.description.abstractThe retinoblastoma protein (pRB), the product of the retinoblastoma gene, is a key regulator of the cell cycle, affecting apoptosis, proliferation and differentiation. Dysregulation of pRB is implicated in the pathogenesis of many cancers, including malignant melanoma. Recently we demonstrated that alpha-melanocyte-stimulating hormone (alpha-MSH)-induced activation of p38 mitogen-activated protein (MAP) kinase leads to differentiation of B16 murine melanoma cells. The current study assesses the ability of alpha-MSH to activate p38 MAP kinase in COLO 853 human melanoma cells and determines whether this is linked to modulation of pRB activity. Treatment of COLO 853 cells with alpha-MSH induced time- and concentration-dependent increases in the phosphorylation of p38 MAP kinase, which corresponded with its ability to induce melanogenesis and inhibit cell growth. SB 203580, a selective inhibitor of p38 MAP kinase, blocked both the alpha-MSH-induced melanogenic response and inhibition of cell growth. Cell cycle analysis using flow cytometry revealed that treatment of COLO 853 cells with alpha-MSH for 72 h led to an increase in the proportion of cells in the G(1) phase and a marked reduction in the amount of phosphorylated pRB. Both of these effects were reversed by pre-treatment of cells with SB 203580. In summary, we have demonstrated for the first time that the alpha-MSH-induced differentiation of COLO 853 human melanoma cells proceeds via a p38 MAP kinase-mediated pathway and is associated with decreased pRB phosphorylation and accumulation of cells in the G(1) phase. (C) 2002 Lippincott Williams Wilkins.en_US
dc.format.extent187 - 192en_US
dc.titleDifferentiation of human melanoma cells through p38 MAP kinase is associated with decreased retinoblastoma protein phosphorylation and cell cycle arresten_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfMELANOMA RESEARCHen_US
pubs.notesaffiliation: Smalley, KSM (Reprint Author), Inst Canc Res, Med Sect, 237 Fulham Rd, London SW3 6JB, England. Inst Canc Res, Med Sect, London SW3 6JB, England. keywords: B16 melanoma; COLO 853; melanccortin; alpha-melanocyte-stimulating hormone; p38 mitogen-activated protein kinase; retinoblastoma keywords-plus: STIMULATING HORMONE; MALIGNANT-MELANOMA; HUMAN MELANOCYTES; MSH PEPTIDES; RECEPTORS; TRANSCRIPTION; INHIBITION; E2F; RB; RESPONSES research-areas: Oncology; Dermatology; Research & Experimental Medicine web-of-science-categories: Oncology; Dermatology; Medicine, Research & Experimental researcherid-numbers: Smalley, Keiran/A-1320-2007 orcid-numbers: Smalley, Keiran/0000-0002-4121-8335 number-of-cited-references: 30 times-cited: 25 usage-count-last-180-days: 0 usage-count-since-2013: 0 journal-iso: Melanoma Res. doc-delivery-number: 567CV unique-id: ISI:000176468600001 da: 2018-09-17en_US
pubs.notesNot knownen_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorEisen, Timen_US

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